Genome-Wide Screening in Haploid Stem Cells Reveals Synthetic Lethality Targeting MLH1 and TP53 Deficient Tumours.

ABSTRACT: Synthetic lethality is defined as a type of genetic interaction where the combination of two genetic events results in cell death, whereas each of them separately does not. Synthetic lethality can be a useful tool in personalised oncology. MLH1 is a cancer-related gene that has a central role in DNA mismatch-repair and TP53 is the most frequently mutated gene in cancer. To identify genetic events that can lead to tumour death once either MLH1 or TP53 is mutated, a genome-wide genetic screening was performed. Thus, mutations in all protein-coding genes were introduced into haploid human embryonic stem cells (hESCs) with and without loss-of-function mutations in the MLH1 or TP53 genes. These experiments uncovered a list of putative hits with EXO1, NR5A2, and PLK2 genes for MLH1, and MYH10 ge

SUBMITTER: Cashman R 

PROVIDER: S-EPMC12584864 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature